This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Currently, there are no FDA-approved medications to treat stimulant addiction. While the acute effects of cocaine on brain function have been well characterized, much less is known about the long-term changes in brain function associated with chronic drug use. Preventing relapse is often the most difficult obstacle in treating drug addiction. It is well recognized that exposure to environmental cues associated with drug use can induce relapse in patients who have been abstinence for extended periods. There is recent evidence that extinction training may have significant efficacy in the treatment of other psychiatric disorders. However, this approach has not been effectively implemented in the context of drug addiction and virtually nothing is known about the neurobiology associated with extinction therapy. Ongoing studies in rhesus monkeys are evaluating changes in brain function following limited- and extended-access to cocaine self-administration, drug abstinence, and extinction training. Cue-induced reinstatement of cocaine self-administration provides an abuse-related behavioral outcome to correlate with neurobiology. Specifically, we are documenting the effects of cocaine exposure and extinction training on resting state and cue-induced functional brain activity with BOLD fMRI. Direct comparisons between abstinence and extinction conditions will validate the usefulness and neurobiological mechanisms of extinction therapy. The research project is highly innovative in its focus on extinction training and functional brain activity in a paradigm that models the progression of cocaine use to dependence and addiction. The long-term goal of our research is to identify targets for effective cocaine pharmacotherapies.